Stiff-Man Syndrome is a rare autoimmune neurological disease that is thought to result from an impairment of GABAergic neurons. A prominent humoral immune response directed against the GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD), occurs in the majority of individuals affected by Stiff-Man Syndrome. By immunohistochemistry we investigated the presence of GAD antibodies in the serum of 3 patients and the cerebrospinal fluid of 1 patient. A variety of dilutions were placed on sections of formalin fixed rat brains. A pattern of fluorescence was revealed in numerous regions of the brain that was identical to that observed when sheep antiserum to GAD was employed. The cerebrospinal fluid also indicated the presence of GAD autoantibodies, although at a lower titer. These results support the notion that the Stiff-Man Syndrome is an autoimmune disease that attacks GABAergic neurons of the CNS. We plan future studies to attempt to create an animal model using the Stiff-Man serum.